In order to understand the causes of diseases such as cancer, Alzheimer's Disease, heart failure, diabetes, or degenerative diseases of the nervous system, it is important to define the gene signals from cells that comprise the diseased brain, heart, muscle, joints, etc. Toward this goal, we are most interested in those cells that have gone astray from the normal function. A diseased body part is made up many cells but it is most important to study how small population of cells in the body can change disease progression. One major mechanism is how genetic signals dictate the abnormal function of critical pathways in disease. Therefore, the ability to define the genetic signals in that small number of cellswhich eventually overcome all normal cellswill define the signals that bring about disease-related pathology. In this grant proposal V investigators are requesting funds to purchase the C1(tm) Single-Cell Auto Prep Systemthe world's first commercially available, automated single-cell isolation and preparation system for a comprehensive genomic analysis. The single cell feature is especially important to our Birmingham VA Medical Center (BVAMC) investigators who study pathologic tissue and body fluid samples from patients that by nature provide small numbers of cells. In this proposal BVAMC research investigators outline a plan to study the molecular inflammatory mechanisms in the development of heart failure, chronic obstructive lung disease (COPD), systemic and pulmonary hypertension, and diabetes-all disorders with high prevalence in our Veteran population. Other BVAMC investigators will study the genetic signatures that seek to discover the underlying mechanisms in the devastating brain tumor glioblastoma multiform and in adult polycystic kidney disease. Finally, BVAMC investigators will study how stem cells and other non-muscle cells within the heart can transform into muscle cells and, thus, regenerate cells lost due to heart attack and prevent heart failure. These studies will serve as a starting point and example for all of our BVAMC investigators in the application of this exciting new technology for many other diseases that will enhance funding capabilities and most importantly fulfill mesh our research goals with our mission of Veteran-centric medical care.